We propose to examine several aspects of the interaction of synaptic membranes of brain and opiates and other drugs of abuse in a continuation of our studies of the past several years. We have found changes in the rates of biosynthesis of cAMP in gross brain areas after an acute injection of morphine to rats. We propose to measure the levels of cAMP and cGMP in sixteen selected areas of rat brain by radioimmunoassay and examine the effects of acute and chronic morphine treatment on these levels. We also propose to measure the turnover of the cyclic nucleotides in the areas that show important changes in cyclic nucleotide levels. We propose to continue our study of the turnover of hypothalamic oligopeptides as affected by opiate treatment. If the 'natural ligand' of the opiate receptor in brain is derived from an anterior pituitary peptide hormone, as seems to be the case, the turnover of pituitary beta-lipotrophin is an important aspect of the turnover of endorphin. We also propose to continue our studies on the effects of opiates and cocaine on the transport of neurotransmitters through the synaptic membrane. We have found an inhibition by morphine of the release of acetylcholine from isolated rat striatal synaptosomes when the release was measured by following radiolabeled acetylcholine appearance in the medium after K plus-stimulation. Since the acetylcholine was labeled by a preincubation with C14-choline, it is possible that the opiate effects were on choline uptake rather than acetylcholine release. We propose to measure total ACh in the synaptosomes and medium by the Goldberg enzyme assay to distinguish between the possibilities of opiate inhibition. BIBLIOGRAPHIC REFERENCES: Clouet, D.H., Gold, G.J. and Iwatsubo, K., Effects of Narcotic Analgesic Drugs on the Cyclic Adenosine 3'5'monophosphate-Adenylate Cyclase System in Rat Brain, Brit. J. Pharmacol. 54, 541-548 (1975). Clouet, D.H. and Iwatsubo, K., Dopamine-sensitive Adenylate Cyclase of the Caudate Nucleus of Rats Treated with Morphine, Life Sci. 17, 35-40 (1975).